After applying Hotfix 4 to an App-V 5.0 SP2 client, not a single application could be launched anymore. The hotfix broke the AppV client!
A virtual application could not be launched from package ‘x’ because the App-V Client Service is not running. Start the App-V Client Service and try again.
To apply Hotfix 4 (HF4) the MSP installer was used (appv_client_kb2956985_x64.msp).
Typical EXE wrapper installers does prerequisite checks (and installs). But as the MSI/MSP was used, these prerequisite checks aren’t executed.
KB2956985 does mention an extra prerequisite, VC++ 2013 Redistributable is necessary since this hotfix!
After installing Microsoft Visual C++ 2013 Redistributable, and rebooting the client, the issue was history.